chr19-38212079-T-G

Position:

• chr19-38212079-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001135155.3(DPF1):​c.1148A>C​(p.Tyr383Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: DPF1 NM_001135155.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85

Genes affected

DPF1 (HGNC:20225): (double PHD fingers 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated; nervous system development; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be part of nBAF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPF1	NM_001135155.3	c.1148A>C	p.Tyr383Ser	missense_variant	12/12	ENST00000355526.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPF1	ENST00000355526.10	c.1148A>C	p.Tyr383Ser	missense_variant	12/12	1	NM_001135155.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1459950 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726090

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.85
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;.;T;.;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;D;D;D;.;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Uncertain	2.2	M;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.7	D;.;D;D;D;.;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0030	D;.;D;D;D;.;D
Sift4G	Uncertain	0.013	D;D;D;D;D;D;D
Polyphen		0.99	D;D;.;P;.;P;.
Vest4		0.58
MutPred		0.41		.;.;.;Gain of disorder (P = 0.003);.;.;.;
MVP		0.76
MPC		1.4
ClinPred		0.95	D
GERP RS		3.3
Varity_R		0.58
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1973470892; hg19: chr19-38702719;